New Depression Treatments in 2026: Spravato, Zuranolone, TMS and What Is Coming Next
New depression treatments explained: esketamine (Spravato), zuranolone, Auvelity, TMS, SAINT and psilocybin research, plus who qualifies and how to start.
The newest depression treatments include esketamine nasal spray (Spravato) for treatment-resistant depression, zuranolone (Zurzuvae), a 14-day pill for postpartum depression, dextromethorphan-bupropion (Auvelity), which can work within one to two weeks, and accelerated TMS protocols such as SAINT. Psilocybin-assisted therapy remains in clinical trials. Most newer options are used after standard antidepressants and therapy have not helped enough.
Key takeaways
- About one in three people with depression do not fully respond to their first two antidepressants.
- Esketamine (Spravato) works on glutamate, not serotonin, and can reduce symptoms within days.
- Auvelity is an oral antidepressant that often starts working faster than SSRIs.
- TMS is non-invasive brain stimulation; accelerated protocols compress treatment into days.
- A psychiatric provider can optimize your current plan before or alongside these newer options.
For decades, depression treatment mostly meant SSRIs and therapy, with weeks of waiting to see if a medication would help. Those treatments still work for many people. But roughly a third of patients do not get relief from their first two medications, and that group drove a wave of research into faster, different-acting treatments.
This guide explains the new depression treatments available today, how they work, who they are for, what to expect from side effects and insurance, and what is still in research. It also covers simpler steps that often get overlooked, such as dose optimization, augmentation, and treating sleep or other conditions that keep depression stuck.
Why newer depression treatments were needed
Traditional antidepressants (SSRIs, SNRIs, bupropion, mirtazapine) mainly act on serotonin, norepinephrine and dopamine. They typically take four to eight weeks to reach full effect. In the large STAR*D trial, only about a third of people reached remission with the first medication, and remission rates dropped with each later step.
When at least two adequate medication trials have not worked, doctors call it treatment-resistant depression (TRD). Newer treatments aim to work faster, act through different brain pathways (such as glutamate and GABA), or bypass medication entirely through brain stimulation.
New depression treatments at a glance
| Treatment | Type | How fast | Best for |
|---|---|---|---|
| Esketamine (Spravato) | Nasal spray, in clinic | Hours to days | Treatment-resistant depression; depression with suicidal thoughts |
| Zuranolone (Zurzuvae) | 14-day oral course | About 3 days | Postpartum depression |
| Dextromethorphan-bupropion (Auvelity) | Daily pill | 1 to 2 weeks | Major depression in adults |
| Brexanolone (Zulresso) | 60-hour IV infusion | Within days | Severe postpartum depression |
| TMS and accelerated TMS (SAINT) | Magnetic brain stimulation | Days (accelerated) to weeks | Depression after medication trials |
| IV ketamine | Off-label infusion | Hours to days | Treatment-resistant depression |
| Psilocybin therapy | Investigational | Days to weeks in trials | Research only (not FDA-approved) |
Esketamine (Spravato): rapid relief for treatment-resistant depression
Spravato is a nasal spray derived from ketamine, approved by the FDA for treatment-resistant depression and for depressive symptoms in adults with acute suicidal thoughts. It has since also been approved for use on its own, not only alongside an oral antidepressant.
- How it works: it blocks NMDA receptors and boosts glutamate signaling, which helps the brain form new connections quickly.
- How it is given: self-administered in a certified clinic, twice weekly at first, then weekly or every other week. You are monitored for two hours and cannot drive that day.
- Side effects: temporary dissociation, dizziness, nausea, sedation and a rise in blood pressure during sessions.
- Cost: often covered by insurance with prior authorization.
Zuranolone (Zurzuvae): a two-week pill for postpartum depression
Approved in 2023, zuranolone is the first oral medication specifically for postpartum depression. It acts on GABA-A receptors, similar to the neurosteroids that drop sharply after birth.
- Taken once nightly with a fat-containing meal for 14 days.
- Many people notice improvement in about three days.
- It causes drowsiness, so you should not drive for 12 hours after a dose.
- It is for depression that begins in the third trimester or within four weeks of delivery.
Learn more about depression treatment at GraceBridge.
Auvelity: a faster-acting oral antidepressant
Auvelity combines dextromethorphan with bupropion. Bupropion slows the breakdown of dextromethorphan, which then acts on NMDA and sigma-1 receptors, a pathway related to ketamine but in pill form. In trials, some people improved within one to two weeks rather than the usual four to six.
It is taken twice daily. Side effects can include dizziness, headache, nausea and dry mouth. Because it contains bupropion, it is not used in people with seizure disorders or certain eating disorders, and it has drug interactions to review with your provider.
TMS and accelerated TMS (SAINT)
Transcranial magnetic stimulation uses magnetic pulses to stimulate the prefrontal cortex, an area that is underactive in depression. Standard TMS involves sessions five days a week for about six weeks. It does not require anesthesia, and you can drive yourself home.
SAINT (Stanford Accelerated Intelligent Neuromodulation Therapy) is an FDA-cleared accelerated protocol: ten short sessions a day for five days, guided by brain imaging. In early studies, a large share of participants with severe treatment-resistant depression reached remission, though availability is still limited.
The most common side effect is scalp discomfort or headache. Seizures are rare.
IV ketamine and psychedelic research
IV ketamine infusions are used off-label for treatment-resistant depression. They can work quickly, but effects may fade without repeated sessions, they are usually not covered by insurance, and quality varies between clinics.
Psilocybin-assisted therapy has shown promising results in clinical trials for treatment-resistant depression, but it is not FDA-approved for depression and should only be accessed through regulated research or programs. Researchers are also studying shorter-acting psychedelics and new neurosteroid medications.
Before you jump to new treatments: steps that often help
Newer is not always the next best step. A thorough psychiatric review often finds simpler fixes:
- Dose optimization: many people are on a dose that is too low or have not stayed on it long enough.
- Switching classes: moving from an SSRI to an SNRI, bupropion or mirtazapine.
- Augmentation: adding medications such as aripiprazole, brexpiprazole, lithium or thyroid hormone.
- Checking the diagnosis: bipolar depression, ADHD, sleep apnea, thyroid disease or low vitamin D can mimic or worsen depression.
- Adding therapy: CBT and behavioral activation boost response to medication.
- Treating sleep: insomnia keeps depression going; CBT for insomnia helps both.
How GraceBridge Psychiatry can help
GraceBridge Psychiatry provides secure online psychiatric care for adults in Texas, Arizona and Washington. Care starts with a comprehensive psychiatric evaluation, followed by a personalized treatment plan that may include therapy referrals, lifestyle strategies and medication management when appropriate. Learn more about how we treat depression. Most new patients are seen within days. See insurance we accept and self-pay pricing.
- Free consultation call: tell us what is going on.
- Book your evaluation: meet a board-certified provider by secure video.
- Get your plan: clear next steps and follow-up until you feel better.
Frequently asked questions
What is the newest treatment for depression?
Recent FDA-approved options include esketamine nasal spray (Spravato), zuranolone (Zurzuvae) for postpartum depression, dextromethorphan-bupropion (Auvelity), and accelerated TMS protocols such as SAINT. Psilocybin therapy is still in clinical trials.
What is treatment-resistant depression?
Depression that has not improved enough after at least two antidepressants taken at adequate doses for adequate time. It is common, and many effective options remain.
How fast does Spravato work?
Some people notice improvement within hours to days of the first sessions, though the full benefit builds over the four-week induction phase.
Is Spravato the same as ketamine?
Spravato is esketamine, one form of the ketamine molecule, given as a nasal spray in a certified clinic. IV ketamine is a different, off-label treatment.
Does insurance cover new depression treatments?
Spravato, TMS, zuranolone and Auvelity are often covered with prior authorization, especially after other treatments failed. IV ketamine and psychedelic therapy usually are not.
What is zuranolone used for?
Zuranolone is a 14-day oral medication approved for postpartum depression. Many people notice improvement within about three days.
Is TMS painful?
TMS feels like tapping on the scalp. Some people have mild headaches or scalp discomfort early on. No anesthesia is needed and you can return to normal activities right after.
What is SAINT TMS?
An accelerated, imaging-guided TMS protocol with ten sessions a day over five days. It is FDA-cleared for treatment-resistant depression.
Is psilocybin approved for depression?
No. Psilocybin is still being studied in clinical trials. It should only be accessed through regulated research or legal programs with medical oversight.
How is Auvelity different from other antidepressants?
It works on NMDA and sigma-1 receptors as well as other pathways and may start working within one to two weeks, faster than most SSRIs.
Are newer depression treatments safe?
They are FDA-approved or cleared based on safety data, but each has specific side effects and monitoring requirements. A psychiatric provider reviews your health history to decide what is appropriate.
What should I try before new depression treatments?
Dose adjustment, switching medication classes, augmentation, therapy and checking for other conditions often help and are usually tried first.
Can I get new depression treatments through telehealth?
Oral options like Auvelity and zuranolone, plus medication management and referrals for Spravato or TMS, can start with an online psychiatric visit. Spravato and TMS themselves are delivered in person.
How do I know if my depression medication is not working?
If you have had little improvement after six to eight weeks at a therapeutic dose, or side effects are hard to tolerate, it is time to review the plan with your provider.
What if I have thoughts of suicide while waiting for treatment?
Call or text 988 in the US for the Suicide and Crisis Lifeline, or go to the nearest emergency room. Rapid-acting treatments like Spravato are specifically studied for this situation.